What was the typical immunosuppression regimen in a kidney transplant (Ktx) study in 2001?

Typical Immunosuppression Regimen in Kidney Transplant Studies Around 2001

The typical immunosuppression regimen in kidney transplant studies around 2001 consisted of triple therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), an antiproliferative agent (azathioprine or mycophenolate mofetil), and corticosteroids, with variable use of induction therapy. 1

Historical Context of 2001 Practice Patterns

Around 2001, kidney transplant immunosuppression was in a transitional period:

• Cyclosporine A (CsA) was still widely used as the primary calcineurin inhibitor, though tacrolimus was gaining acceptance after its FDA approval in 1994 for kidney transplantation 2
• Azathioprine remained common as the antiproliferative agent, though mycophenolate mofetil (MMF) was increasingly replacing it after demonstrating superior outcomes in trials from the late 1990s 3
• Corticosteroids were universally included in maintenance regimens, with steroid-free protocols not yet widely adopted 3

Induction Therapy Patterns

Induction therapy use was inconsistent in 2001:

• Antithymocyte globulin (ATG) was the most common induction agent when used, particularly for high-risk patients 2
• IL-2 receptor antagonists (daclizumab, basiliximab) were newly available but not yet standard practice, having been approved in the late 1990s 2
• Many centers performed transplants without any induction therapy, relying solely on maintenance immunosuppression 2

Maintenance Immunosuppression Components

Calcineurin Inhibitors

• Cyclosporine microemulsion (Neoral) was the dominant CNI in most protocols around 2001 2
• Tacrolimus was used in approximately 20-30% of cases, often reserved for patients with cyclosporine intolerance or acute rejection 2
• Initial tacrolimus dosing when used was typically 0.1-0.2 mg/kg/day divided every 12 hours 1

Antiproliferative Agents

• Azathioprine (1-2 mg/kg/day) remained in widespread use despite emerging evidence favoring MMF 3, 4
• Mycophenolate mofetil was increasingly adopted at doses of 1-2 grams daily, particularly in newer protocols 2

Corticosteroids

• Prednisone was universally included, typically starting at high doses (0.5-1 mg/kg/day) and tapering to maintenance doses of 5-10 mg/day 3
• Early steroid withdrawal was not practiced in 2001, as this approach only gained evidence-based support in subsequent years 3

Common Pitfalls in 2001-Era Protocols

• Higher tacrolimus target levels (10-15 ng/mL) were used, which we now recognize as unnecessarily nephrotoxic 1
• Inadequate CMV prophylaxis was common, particularly in high-risk donor-positive/recipient-negative combinations 2
• mTOR inhibitors (sirolimus, everolimus) were just entering clinical use and not part of standard protocols 4

Evolution Since 2001

Current evidence-based practice has evolved significantly:

• Induction therapy with IL-2 receptor antagonists is now standard for most recipients 3, 1
• Tacrolimus has replaced cyclosporine as first-line CNI based on superior efficacy 3, 1
• Mycophenolate has replaced azathioprine as the preferred antiproliferative agent 3, 1
• Early steroid withdrawal is now acceptable in low-risk patients receiving induction therapy 3